单位：[1]Laboratories of Stem Cell Biology and Regenerative Medicine, Experimental Research Center and Neurological Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China医技科室北京市临床医学研究所实验中心首都医科大学附属北京友谊医院[2]Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA[3]Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA
Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 mg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls. Wnt-3a intranasal treatment of seven days upregulated the expression of brain-derived growth factor (BDNF), increased the proliferation and migration of neuroblasts from the subventricular zone (SVZ), resulting in increased numbers of newly formed neurons and endothelial cells in the peri-infarct zone. Both the molecular and cellular effects of Wnt-3a were blocked by the Wnt specific inhibitors XAV-939 or Dkk-1. In functional assays, Wnt-3a treatment enhanced the local cerebral blood flow (LCBF) in the peri-infarct, as well as improved sensorimotor functions in a battery of behavioral tests. Together, our data demonstrates that the Wnt-3a signaling can act as a dual neuroprotective and regenerative factor for the treatment of ischemic stroke.
基金：
NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NS075338, NS085568, NS091585]; American Heart Association (AHA)American Heart Association; AHA Postdoctoral FellowshipAmerican Heart Association [POST25710112]; NIH Predoctoral FellowshipUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32 007480-15]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81500989]; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS091585] Funding Source: NIH RePORTER
第一作者单位：[1]Laboratories of Stem Cell Biology and Regenerative Medicine, Experimental Research Center and Neurological Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China[2]Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA
共同第一作者：
通讯作者：
通讯机构：[1]Laboratories of Stem Cell Biology and Regenerative Medicine, Experimental Research Center and Neurological Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China[2]Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA[3]Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA[*1]School of Medicine, Emory University, 101 Woodruff Circle, WMB 617, Atlanta, GA 30322, USA
推荐引用方式(GB/T 7714)：
Wei Zheng Zachory,Zhang James Ya,Taylor Tammi M.,et al.Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice[J].JOURNAL of CEREBRAL BLOOD FLOW and METABOLISM.2018,38(3):404-421.doi:10.1177/0271678X17702669.
APA：
Wei, Zheng Zachory,Zhang, James Ya,Taylor, Tammi M.,Gu, Xiaohuan,Zhao, Yingying&Wei, Ling.(2018).Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice.JOURNAL of CEREBRAL BLOOD FLOW and METABOLISM,38,(3)
MLA：
Wei, Zheng Zachory,et al."Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice".JOURNAL of CEREBRAL BLOOD FLOW and METABOLISM 38..3(2018):404-421
